PROJECT ABSTRACT Research Domain Criteria (RDoC) is a breakthrough framework for understanding the etiology of mental disorders, but it has no clinical traction at present. Of the RDoC units of analysis, self-report measures can be most feasibly implemented in a clinic, but many self-reports for RDoC?s Negative Valence Systems (NVS) constructs have psychometric shortcomings and lack normative data. We seek to develop psychometrically sound, brief, and validated self-report measures (questionnaires and interviews) of each NVS construct with strong normative data. We will investigate linkages of these self-report measures to other RDoC units of analyses (behavior, task performance, and psychophysiology) to identify self-reports that align with NVS dimensions most strongly and specifically. Also, we will fully characterize clinical manifestations of NVS constructs using a comprehensive dimensional system of symptoms, maladaptive traits, and behaviors (Hierarchical Taxonomy of Psychopathology; HiTOP). The direct counterpart of NVS is internalizing psychopathology, which HiTOP describes with high resolution using 36 specific dimensions. Measure development will be carried out in 2 successive phases, each including a sample of (a) 400 outpatients in psychiatric clinics and (b) 600 community-dwellers. Participants will be adults selected to be representative of the US adult population in terms of age, sex, and ethnicity to obtain good normative data. In Phase 3, we will validate self-report measures against physiology, task performance, and behavior markers of NVS aligned with the RDoC matrix in a new sample of 300 community adults and 300 psychiatric outpatients. To facilitate rapid and ethnically diverse data collection, three recruitment sites?Buffalo NY, Stony Brook NY, and Dallas/Denton TX?are proposed. The proposed research will provide a comprehensive catalogue of self-reported characteristics linked to NVS. This will produce stronger measures of NVS constructs and a cross-walk to their clinical manifestations, which will enable clinical translation of NVS. The resulting instruments will be normed, reliable, and highly efficient, and thus scalable to mobile monitoring, screening, and self-administration at population level and clinically. The rigorous and systematic linkage between RDoC NVS constructs and HiTOP internalizing dimensions will be the first step to bringing RDoC and HiTOP together into a unified and evidence- based nosology that integrates etiologic and clinical characterizations of patients.